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Kaletra Once A Day
Reported by Jules Levin
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Tomorrow, thursday, is the last day of the Conference. and the Late Breaker
oral session on thursday from 9-11:45am is the only presentation session
left. There is a report on rosigltazone & lipoatrophy, and a report of an
interim analysis of the ACTG study of Pegasys+ribavirin for HCV/HIV
coinfected patients. Today, two studies were reported on adefovir for HBV in
3TC resistant patients. The viral load reductions were good and observers
were impressed with the HBV suppression by one drug, adefovir. FDA approval
is expected for HBV later this year. An expanded access program is expected
soon in the USA.
Here are some highlights from today. More detailed reports will follow.
Rick Bertz from Abbott reported in an oral session the results from a pilot
study comparing Kaletra once daily to twice daily. Previously, its been
reported from a study that Kaletra (400 mgLpv/100 mg RTV) plus nukes had 76%
of patients <50 copies/ml (ITT) after 144 weeks in treatment naive patients.
This study was to assess pharmacokinetics (blood levels), safety,
tolerability and antiviral activity. Patients were randomized to receive
Kaletra (400/100) 3 capsules twice daily + d4T/3TC administered with food
(n=19) or Kaletra 800/200 (6 caps) once daily plus d4T/3TC administered with
food (n=19). Blood samples of blood levels were taken at 0, 2, 4, 6, 8, & 12
hrs, and 24 hrs for QD at three weeks on drug. And trough sampling was done
at weeks 8, 16, 24 & 48.
Viral load was 50,000 and CD4s 250. There was not much difference in adverse
events & grade 3/4 lab abnormalitiies between the two regimens: diarrhea 1 in
each arm; nausea 3 in QD, 1 in BID; asthenia 2 in BID, 0 in QD; cholesterol
>200, 1 in each arm; triglycerides >750, 2 in QD, 1 in BID. 3 patients
discontinued in BID arm, 1 in QD. The viral load reductions were similar for
both groups at week 48: 79% for the BID group & 74% for the QD group (ITT,
m=f). CD4s increased >200 in both groups. The AUC (overall blood levels) were
similar for the 2 arms. The average Cmin (lowest levels of drug in blood
during dose period) was lower in QD regimen (2.46 ug/ml vs 5.51 ug/ml) and
this difference was statistically significant. The median Ctrough was also
significantly lower for the QD group. The overall median Kaletra Ctrough/IC50
(drug blood levels/over level needed to suppress HIV) (protein-binding
adjusted) was 40 for the QD regimen vs 84 for the BID regimen. In addition,
there was much more variability in Ctrough levels among the individual
patients receiving the once-daily regimen. Some patients receiving QD had
lower Ctrough levels while all patients receiving BID had bunched together
higher levels. Two patients on QD regimen had Kaletra Ctrough/IC50 (IQ) <10.
The lowest IQ in BID regimen was 36. Although drug blood levels were on
average lower in QD regimen they were still what appeared to be well above
the levels needed to suppress HIV (IC50).
The 4 Kaletra failures (>400) had no genotypic or phenotypic Kaletra
resistance as has been observed in other Kaletra studies. But 3TC resistance
was seen.
In sum, the once daily (QD) regimen was well tolerated in this preliminary
pilot study, and antiral activity appeared equal in both arms. The presenter
said that twice daily is the preferable way to take Kaletra but for Direct
Observed Therapy or other unique situations this once daily regimen may be
useful. Additional research studies still need to be conducted to confirm
these results.
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